MqsR/MqsA Toxin/Antitoxin System Regulates Persistence and Biofilm Formation in KT2440.

Bacterial toxin/antitoxin (TA) systems have received increasing attention due to their prevalence, diverse structures, and important physiological functions. In this study, we identified and characterized a type II TA system in a soil bacterium KT2440. This TA system belongs to the MqsR/MqsA family. We found that PP_4205 (MqsR) greatly inhibits cell growth in KT2440 and , the antitoxin PP_4204 (MqsA) neutralizes the toxicity of the toxin MqsR, and the two genes encoding them are co-transcribed. MqsR and MqsA interact with each other directly and MqsA is a negative regulator of the TA operon through binding to the promoter. Consistent with the MqsR/MqsA pair in , the binding of the toxin MqsR to MqsA inhibits the DNA binding ability of MqsA in KT2440. Disruption of the gene which induces expression increases persister cell formation 53-fold, while overexpressing which represses expression reduces persister cell formation 220-fold, suggesting an important role of MqsR in persistence in KT2440. Furthermore, both MqsR and MqsA promote biofilm formation. As a DNA binding protein, MqsA can also negatively regulate an ECF sigma factor AlgU and a universal stress protein PP_3288. Thus, we revealed an important regulatory role of MqsR/MqsA in persistence and biofilm formation in KT2440.